delta-unsaturated d-homosteroids and process



United States Patent he in either the aor fl-configuration. When X and x' are both A -UNSATURATED D-HOMOSTEROIDS AND PROCESS Raymond 0. Clinton, North Greenbush, N. Y., assignor to Sterling Drug Inc., New York, N. Y., a corporation of Delaware No Drawing. Application January 14, 1954 10 Serial No. 404,123

6 Claims. (Cl. 260-488) This invention relates to new tetracyclic compounds of the hydrochrysene series having the formula 12 "I 1113 17 c D 14 1e 1 9 15 2 10 8 a a 7 n X 4 a I wherein X and X are selected from the class consisting of =0, and H l wherein X and X have the same meanings as given above. The intermediates of Formula II are prepared as described in my copending application, Serial No. 333,615, filed January 27, 1953, and now abandoned.

The dehydration of the compounds of Formula II is carried out by treating them with boron trifluoride, conveniently in the form of its ether complex, in acid medium. The acid medium is one in which the tetracyclic compound is soluble and which is inert to the action of boron trifluoride, such as a lower fatty acid; a preferred acid is acetic acid. The dehydration reaction takes place readily at room temperature.

In the above general Formula I, the groups X and X each represent either a single divalent group, the oxygen portion of a carbonyl group (=0); or two monovalent groups, hydrogen and a hydroxy group or acyloxy group LOB ii...)

The groups X and X can be the same or different, and when hydroxy or acyloxy groups are present they can H -OR the acyl groups R can be the same or difierent.

The nature of the acyl groups is not critical as they are used only as blocking or protecting means for the hydroxy groups, and exert no influence upon any physiological properties inherent in the uneste'rified compounds.

The preferred types of acyl groups are those derived from lower fatty acids, including lower-alkanoic acids, loweraliphatic dicarboxylic acids and monocyclic aromatic carboxylic acids, optionally substituted by one or more inert groups such as nitro, alkyl, alkoxy and halogen. Thus R in the above definition can be lower-alkenoyl, such as formyl, acetyl, propionyl, butyryl, valeryl, isovaleryl, caproyl, etc., wherein the alkanoyl group has from 1 to about 6 carbon atoms; carboxy-lower-alkanoyl, such as succinyl, glutaryl and adipyl; and monocyclic aroyl, such as benzoyl, p-toluyl and p-nitrobenzoyl.

The compounds of Formula I can belong either to the normal series (A/B cis) or the allo series (A/B trans).

My new compounds are useful as intermediates in the preparation of compounds having hormonal properties, for example, 11-hydroxy-9-chloro compounds which are known in the steroid series to possess high cortisone-like activity. This transformation can be effected by reaction of the compounds of the invention with a peroxidic compound to give the 9(11)-epoxide, followed by cleavage with hydrogen chloride.

The following examples will further illustrate the invention.

EXAMPLE 1 D-homoetioch0lane-3u,115,17afl-triol (4.5 g.) was dissolved in ml. of glacial acetic acid by gentle heating. The solution was cooled to room temperature, 5.0 ml. of boron trifluoride ether complex was added, and the mixture was allowed to stand at room temperature for nineteen hours. The mixture was then diluted with water and extracted with an ether-ethyl acetate mixture. The organic layer was separated, washed with water and concentrated to dryness. Ethanol was added to the residue and concentrated to dryness to remove residual ethyl acetate. The crystalline residue was taken up in ml. of methanol, 6 g. of potassium carbonate in 25 ml. of

water was added, and the mixture was refluxed for one and one-half hours in order to saponify any acetylated hydroxy groups produced during the reaction. Water was added to produce a total volume of one liter and the product was collected by filtration, washed with water and dried. The 3.6 g. of material thus obtained was recrystallized three times from ethyl acetate and dried for seven hours at 100 C. in a vacuum oven, given 9(11)- D-homoetiocholene-3a,17af3-diol, M. P. 2l52l7.5 C. (corr.), [a] =+10.9 (1% in dioxane).

Analysis.--Calcd. for C H5 O C, 78.89; H, 10.59.

Found: C, 79.02; H, 10.60.

EXAMPLE 2 3a-acet0xy-9(1I -D-homoeti0cholen-1 7a-0ne A mixture of 4.00 g. of 3u-acetoxy-D-homoetiocholan- 11/3-ol-17a-one and 5 cc. of boron trifluoride ether complex and 25 cc. of glacial acetic acid was allowed to stand at room temperature for about sixteen hours. The reacl ate nted eb. 4, 1958 ,3 timltmiztute. diluted with 75 cc. of. water, and the solid which separated was collected by filtration and dried, giving 3.84 g. of 3a-acetoxy-9(11)-D-homoetiocholentions from ethyl acetate a sample melting at 177-179 C. (corn) was obtained; [a] =|12.6 (1% in chloroform).

EXAMPLE 3 can be prepared bytreating D-homoetiocholane-l15,172. 8-

diol-3'-one with boron trifiuoride ether complex in acetic EXAMPLE 5 3a-benzoyl0xy-9, (.11 -D-hom0e!ioch0len-1 7a-0ne can beprepared by treating 3a-benzoyloxy-D-homoetio cholan-llB-ol-Ua-one with boron trifiuoride ether compic in accticacid according to the manipulative procedure described above in Example 2.

I claim: 1. A compound having the formula whercinX andX are selected from the class consisting of i =0, H H

011 011 wherein R is a carboxylic acyl group having from 1 to aboutS carbon atoms.

2. A compound having the formula and 3i CA QQmPQDQdhEWiBg the formula CHI 4. 9( l 1 .-D.-homoetiocholene-3c, l'Iap-diol. 5. 3a-acetoxy-9( l 1 )-D-homoetiocholcn-17a-one.

6. The processfor preparing acompound having the formula wherein X and X are selected from the class consisting of Lee and

L-OR

'wherein R is a carboxylic acyl group having from 1 to about 8 carbon atoms which comprises treating a com- P und h vin the fiorm l in which the 11 -hy droxy group is in the fi-configuration with boron trifluoride in acid medium.

References Cited in the file of this patent UNITED STATES PATENTS Ruzicka et a]. Iuly 20, 1943 Ruzicka et a1 June 20, 1944 OTHER REFERE CE ShQPPQCetBLI Chm. Abst. 38 (1944.), 4.615. Jones et al.: I. Am. Chem. Soc. 73 ,(1951), 3216.

as A 

1. A COMPOUND HAVING THE FORMULA 